ABCC9

ATP binding cassette subfamily C member 9, the group of ATP binding cassette subfamily C

Basic information

Region (hg38): 12:21797389-21942543

Links

ENSG00000069431 ∙ NCBI:10060 ∙ OMIM:601439 ∙ HGNC:60 ∙ Uniprot:O60706 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrichotic osteochondrodysplasia Cantu type (Definitive), mode of inheritance: AD
• Brugada syndrome (Limited), mode of inheritance: AD
• hypertrichotic osteochondrodysplasia Cantu type (Strong), mode of inheritance: AD
• dilated cardiomyopathy 1O (Moderate), mode of inheritance: AD
• dilated cardiomyopathy 1O (Limited), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• acromegaloid facial appearance syndrome (Supportive), mode of inheritance: AD
• hypertrichosis-acromegaloid facial appearance syndrome (Supportive), mode of inheritance: AD
• hypertrichotic osteochondrodysplasia Cantu type (Supportive), mode of inheritance: AD
• hypertrichotic osteochondrodysplasia Cantu type (Strong), mode of inheritance: AD
• intellectual disability and myopathy syndrome (Limited), mode of inheritance: AR
• dilated cardiomyopathy 1O (Strong), mode of inheritance: AD
• atrial fibrillation, familial, 12 (Limited), mode of inheritance: Unknown
• intellectual disability and myopathy syndrome (Limited), mode of inheritance: AR
• dilated cardiomyopathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1O; Atrial fibrillation, familial 12; Cantu syndrome; Intellectual disability and myopathy syndrome	AD/AR	Cardiovascular	Surveillance for related cardiac complications, which have been reported to include cardiomyopathy and arrhythmias, may allow early medical intervention, decreasing morbidity and mortality; Cantu syndrome, which may be clinically recognizable,can include cardiovascular malformations that would benefit from surveillance/intervention similar to other ABCC9-related disorders	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	15034580; 16563363; 17245405; 22610116; 22608503; 31575858
Though manifestations have been described in adults, surveillance and interventions should likely begin in the pediatric period

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCC9 gene.

• not provided (4 variants)
• Dilated cardiomyopathy 1O (4 variants)
• Hypertrichotic osteochondrodysplasia Cantu type (4 variants)
• ABCC9-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCC9 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	325	4	337
missense	8	19	530	3		560
nonsense			22	1		23
start loss			1			1
frameshift			37			37
inframe indel			10			10
splice donor/acceptor (+/-2bp)			35			35
splice region			74	76	5	155
non coding			55	275	109	439
Total	8	19	698	604	113

Variants in ABCC9

This is a list of pathogenic ClinVar variants found in the ABCC9 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-21801025-A-G		not specified	Benign (Nov 21, 2016)
12-21801037-C-T		ABCC9-related disorder	Likely benign (Nov 17, 2022)
12-21801039-C-G		not specified	Uncertain significance (Aug 17, 2015)
12-21801056-G-A		Cardiomyopathy	Likely benign (Jun 01, 2020)
12-21801057-C-A		Primary dilated cardiomyopathy	Uncertain significance (Feb 10, 2015)
12-21801064-A-C			Uncertain significance (May 02, 2019)
12-21801066-G-C			Uncertain significance (Nov 30, 2022)
12-21801090-G-GC		See cases	Uncertain significance (Feb 13, 2023)
12-21801125-A-G		not specified • ABCC9-related disorder	Likely benign (Apr 04, 2013)
12-21801157-C-T		Dilated cardiomyopathy 1O	Pathogenic (Apr 01, 2004)
12-21801158-C-T			Likely benign (Dec 21, 2018)
12-21801159-G-A		Dilated cardiomyopathy 1O;Atrial fibrillation, familial, 12	not provided (-)
12-21804904-T-G			Likely benign (Jun 14, 2018)
12-21805172-G-A		not specified	Uncertain significance (Jul 14, 2021)
12-21805174-C-G		Dilated cardiomyopathy 1O • Hypertrichotic osteochondrodysplasia Cantu type;Dilated cardiomyopathy 1O;Atrial fibrillation, familial, 12;Intellectual disability and myopathy syndrome	Uncertain significance (Apr 28, 2023)
12-21805174-C-T		Dilated cardiomyopathy 1O	Likely benign (Nov 08, 2022)
12-21805180-G-C		Dilated cardiomyopathy 1O	Uncertain significance (Oct 04, 2022)
12-21805183-G-T		Dilated cardiomyopathy 1O	Likely benign (Nov 14, 2022)
12-21805184-G-A		Atrial fibrillation, familial, 12 • Cardiomyopathy • Hypertrophic cardiomyopathy • Dilated cardiomyopathy 1O	Uncertain significance (Oct 17, 2022)
12-21805193-A-G		Dilated cardiomyopathy 1O	Conflicting classifications of pathogenicity (Jul 06, 2022)
12-21805196-G-A		Dilated cardiomyopathy 1O	Uncertain significance (Sep 14, 2021)
12-21805197-T-C		Dilated cardiomyopathy 1O	Uncertain significance (Aug 30, 2022)
12-21805211-T-C		not specified • Dilated cardiomyopathy 1O	Uncertain significance (Jan 14, 2023)
12-21805214-T-C		Dilated cardiomyopathy 1O • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Feb 02, 2024)
12-21805216-G-A		Dilated cardiomyopathy 1O	Likely benign (Apr 17, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCC9	protein_coding	protein_coding	ENST00000261200	38	144002

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.35e-9	1.00	125610	0	138	125748	0.000549

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.97	432	836	0.516	0.0000439	10136
Missense in Polyphen		73	222.86	0.32757		2745
Synonymous	0.00745	298	298	0.999	0.0000160	3023
Loss of Function	5.49	30	84.4	0.355	0.00000426	1009

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000525	0.000525
Ashkenazi Jewish	0.000120	0.0000992
East Asian	0.000218	0.000217
Finnish	0.00205	0.00203
European (Non-Finnish)	0.000459	0.000457
Middle Eastern	0.000218	0.000217
South Asian	0.000491	0.000490
Other	0.000819	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with KCNJ11. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation. {ECO:0000269|PubMed:9831708}.
• Disease: DISEASE: Cardiomyopathy, dilated 1O (CMD1O) [MIM:608569]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:15034580}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Atrial fibrillation, familial, 12 (ATFB12) [MIM:614050]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:17245405}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hypertrichotic osteochondrodysplasia (HTOCD) [MIM:239850]: A rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. The hypertrichosis leads to thick scalp hair, which extends onto the forehead, and a general increase in body hair. In addition, macrocephaly and coarse facial features, including a broad nasal bridge, epicanthal folds, a wide mouth, and full lips, can be suggestive of a storage disorder. About half of affected individuals are macrosomic and edematous at birth, whereas in childhood they usually have a muscular appearance with little subcutaneous fat. Thickened calvarium, narrow thorax, wide ribs, flattened or ovoid vertebral bodies, coxa valga, osteopenia, enlarged medullary canals, and metaphyseal widening of long bones have been reported. Cardiac manifestations such as patent ductus arteriosus, ventricular hypertrophy, pulmonary hypertension, and pericardial effusions are present in approximately 80% of cases. Motor development is usually delayed due to hypotonia. Most patients have a mild speech delay, and a small percentage have learning difficulties or intellectual disability. {ECO:0000269|PubMed:22608503, ECO:0000269|PubMed:22610116, ECO:0000269|PubMed:26621776}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: ABC transporters - Homo sapiens (human);Antiarrhythmic Pathway, Pharmacodynamics;Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;Ion homeostasis;Transport of small molecules;Neuronal System;Cardiac conduction;Muscle contraction;ABC-family proteins mediated transport;ATP sensitive Potassium channels;Inwardly rectifying K+ channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.157

Intolerance Scores

• loftool: 0.0477
• rvis_EVS: -1.97
• rvis_percentile_EVS: 1.82

Haploinsufficiency Scores

• pHI: 0.112
• hipred: Y
• hipred_score: 0.671
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.762

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Abcc9
• Phenotype: growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: potassium ion transport;response to drug;defense response to virus;transmembrane transport;ATP hydrolysis coupled anion transmembrane transport;potassium ion import across plasma membrane
• Cellular component: plasma membrane;inward rectifying potassium channel;membrane;sarcomere;sarcolemma
• Molecular function: transporter activity;potassium channel activity;ATP binding;sulfonylurea receptor activity;potassium channel regulator activity;ATPase activity, coupled to transmembrane movement of substances;ATPase-coupled anion transmembrane transporter activity;ion channel binding